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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1992-12-24
pubmed:abstractText
The insulin-like growth factor I receptor (IGF-I-R) gene is expressed in most body tissues. The levels of IGF-I-R mRNA, however, are regulated by a number of physiological conditions (development, differentiation, and hormonal milieu) as well as in certain pathological states (diabetes and tumors). To understand the molecular mechanisms which control the transcription of the IGF-I-R gene, we have cloned the promoter of the rat receptor gene and have characterized its activity by transient expression assays. Different fragments of the 5'-flanking region (subcloned upstream of a luciferase reporter gene) were transfected into buffalo rat liver 3A cells (a cell line with a low number of IGF-I binding sites) and Chinese hamster ovary cells (a cell line with a higher number of cell-surface receptors). In both cell lines, most of the promoter activity was located in the proximal 416 base pairs of 5'-flanking region. However, further dissection of this proximal fragment revealed a cell type-specific pattern of promoter activity. Thus, in buffalo rat liver 3A cells, subfragments of this region each contributed to total activity, suggesting that contiguous cis-elements can act together to activate transcription. In Chinese hamster ovary cells, on the other hand, subfragments of the proximal promoter region partially substituted for the proximal 416 base pairs of 5'-flanking region. Coexpression studies using an IGF-I-R promoter reporter construct together with an Sp1 expression vector (under the control of an ADH promoter) were performed in SL2 cells, a Drosophila cell line which lacks endogenous Sp1. The results obtained showed that Sp1 can trans-activate the IGF-I-R promoter in vivo. Transient transfection assays were complemented with gel-retardation assays and DNase I footprinting experiments, which showed that transcription factor Sp1 is potentially an important regulator of IGF-I-R gene expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1545-58
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:1448110-Animals, pubmed-meshheading:1448110-Base Sequence, pubmed-meshheading:1448110-CHO Cells, pubmed-meshheading:1448110-Cell Line, pubmed-meshheading:1448110-Cloning, Molecular, pubmed-meshheading:1448110-Cricetinae, pubmed-meshheading:1448110-Deoxyribonuclease I, pubmed-meshheading:1448110-Liver, pubmed-meshheading:1448110-Luciferases, pubmed-meshheading:1448110-Molecular Sequence Data, pubmed-meshheading:1448110-Oligonucleotide Probes, pubmed-meshheading:1448110-Plasmids, pubmed-meshheading:1448110-Promoter Regions, Genetic, pubmed-meshheading:1448110-RNA, Messenger, pubmed-meshheading:1448110-Rats, pubmed-meshheading:1448110-Rats, Inbred BUF, pubmed-meshheading:1448110-Receptor, IGF Type 1, pubmed-meshheading:1448110-Recombinant Proteins, pubmed-meshheading:1448110-Transcription, Genetic, pubmed-meshheading:1448110-Transfection
pubmed:year
1992
pubmed:articleTitle
Structural and functional analysis of the insulin-like growth factor I receptor gene promoter.
pubmed:affiliation
Section on Molecular and Cellular Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't